PRECIFIT

Posology Treatment with Precifit primarily focuses on individualized therapy using either the pre-filled dose dispenser OraFID or the dose dispenser MyFID. The optimum daily dosage of levodopa/carbidopa must be determined by careful titration in each patient.

Precifit is available as small dose tablets, in a ratio of 1:4 of carbidopa to levodopa, to facilitate precise dosage for each patient. General Considerations Studies show that the peripheral dopa-decarboxylase is fully inhibited (saturated) by carbidopa at doses between 70 and 100 mg a day.

Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting. Standard antiparkinsonian drugs, other than levodopa alone, may be continued while carbidopa/levodopa is being administered, although their dosage may have to be adjusted.

Patients should be carefully monitored during the dosage adjustment period. Involuntary movements, particularly blepharospasm, are a useful early sign of excess dosage in some patients. Dosage may be best initiated with a 100/25 dose three times a day.

This dosage schedule provides 75 mg of carbidopa per day. 5- 100/25 mg of Precifit every day or every other day, as necessary, maximum until a dosage equivalent of 800/200 mg of Precifit a day is reached. Response has been observed in one day, and sometimes after one dose.

Fully effective doses usually are reached within seven days as compared to weeks or months with levodopa alone. Precifit tablets may be used for dosage titration according to the needs of the individual patient. Maintenance Therapy with Precifit should be individualized and adjusted gradually according to response.

Patients who experience fluctuations in response and end of dose effect (wearing-off) may be helped by dividing the dosage into smaller, more frequent dosing without, however, altering the total daily dose. If necessary, the dosage of Precifit may be increased to a maximum of 2000/500 mg a day.

Experience with a total daily dosage greater than 200 mg carbidopa is limited. Patients receiving levodopa with another decarboxylase inhibitor Begin with a dosage of Precifit that will provide the same amount of levodopa as contained in the other levodopa/decarboxylase inhibitor combination.

Patients receiving other antiparkinsonian agents Current evidence indicates that other antiparkinsonian agents may be continued when carbidopa/levodopa is introduced, although dosage may have to be adjusted in line with manufacturer’s recommendations.

Use in the elderly There is wide experience in the use of levodopa/carbidopa in elderly patients. The recommendations set out above reflect the clinical data derived from this experience. Patients with renal impairment Impact of renal function on levodopa/carbidopa clearance is limited.

Precifit should be administered cautiously to patients with renal impairment. The dose should be titrated individually. Patients with hepatic impairment Precifit should be administered cautiously to patients with mild to moderate hepatic impairment.

The dose should be titrated individually. Paediatric population The safety of Precifit in patients under 18 years has not been established. There is no relevant use of Precifit in children and adolescents in the indication of patients with idiopathic Parkinson's disease.

Method of administration Oral use. The tablets should be dissolved in half a glass of water. When dissolved, a whitish dispersion is formed within a few minutes. Intake should be done immediately after dissolution. The tablets (small tablets, each with a low dose of levodopa/carbidopa) are administered either by a pre-filled dose dispenser called OraFID or with a separately provided dose dispenser, called MyFID.

Both dose dispensers deliver individualized dose based on the number of tablets dispensed. Precifit in a pre-filled dose dispenser, OraFID OraFID dispenses the correct number of tablets as long as there are tablets needed for a full dose left in the container.

The OraFID container is disposable and should not be refilled. OraFID contains 2 250 dispersible tablets. The dose dispenser can dispense 1-20 tablets per withdrawal. With a total daily dosage of 300–400 mg levodopa, the OraFID pre-filled dose dispenser will last about four to five weeks.

Precifit cartridges in MyFID dose dispenser The MyFID dose dispenser is loaded with a cartridge containing 750 dispersible tablets. The MyFID dose dispenser has a reminder function to facilitate dosage compliance. The dose dispenser is also equipped with a system for dose recording and symptom rating from which data can be transmitted to the treating physician.

At total daily dosages of 300–400 mg levodopa one cartridge lasts for about a week and a half. When the cartridge is empty, it can easily be replaced by the patient. For further information, see the manual of the dose dispenser.

Intake with food and drink:

If possible, Precifit should be taken 30 minutes before or 1 hour after meals. Intake of Precifit with protein-rich food can reduce the effect.

Summary of the safety profile Side effects that occur frequently with carbidopa/levodopa are those due to the central neuropharmacological activity of dopamine. These reactions can usually be diminished by dosage reduction. The most common are dyskinesias including choreiform, dystonic and other involuntary movements and nausea.

Muscle twitching and blepharospasm may be taken as early signs to consider dosage reduction. Tabulated list of adverse reactions Adverse events classified by MedDRA convention and frequency; Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); no known frequency (cannot be estimated from the available data).

) and has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes, numbness Eye disorders Blurred vision, blepharospasm , activation of a latent Horner's syndrome, diplopia, dilated pupils, and oculogyric crises.

Cardiac disorders Palpitations, irregular heartbeat Vascular disorders Orthostatic hypotension including hypotensive episodes Hypertensi on, hot flashes Phlebitis, blushing Respiratory, thoracic and mediastinal Hoarseness, abnormal breathing Dyspnoea, hiccups MedDRA System Organ Class Very common (≥1/10) Common (≥ 1/100 to < 1/10) Uncommo n (>1/1,000 to <1/100) Rare (>1/10,000 to <1/1,000) Very rare (<1/10,000) not known (cannot be estimated from the available data) disorders pattern Gastrointestin al disorders Nausea, vomiting, bitter taste Constipatio n, diarrhoea, sialorrhoea, dysphagia, flatulence, gastrointest inal pain and discomfort, dry mouth Dyspepsia, dark saliva, gastrointestina l bleeding, burning sensation of the tongue, duodenal ulceration Skin and subcutaneous tissue disorders Hypersensitivi ty reactions including urticaria, pruritus, facial redness, hair loss, rash, increased sweating, dark sweat and Henoch- Schonlein purpura Musculoskelet al and connective tissue disorders Muscle spasms, convulsions , muscle twitching Trismus Muscle twitching Renal and urinary disorders Dark urine Urinary retention, urinary incontinence Reproductive system and breast disorders Priapism General disorders and administration site conditions Asthenia, weakness, malaise, oedema, fatigue Chest pain Description of selected adverse reactions Dopamine Dysregulation Syndrome (DDS) is an addictive disorder seen in some patients treated with carbidopa/ levodopa.

4). 4) Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard

Precifit is not recommended for the treatment of drug-induced extrapyramidal reactions. Precifit should be administered cautiously to patients with severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease, or history of peptic ulcer disease (because of the possibility of upper gastro-intestinal haemorrhage).

Care should be exercised when Precifit is administered to patients with a history of myocardial infarction who have residual atrial nodal, or ventricular arrhythmias. Cardiac function should be monitored with particular care in such patients during the period of initial dosage adjustment.

A dosage reduction of antihypertensive treatment may be necessary. If a COMT inhibitor is added to Precifit, it can be necessary to lower the dose of Precifit. Precifit may induce orthostatic hypotension. Therefore Precifit should be given cautiously to patients who are taking other medicinal products which may cause orthostatic hypotension.

All patients should be monitored carefully for the development of mental changes, depression with suicidal tendencies, and other serious antisocial behaviour. Patients with current psychoses should be treated with caution. As with levodopa, Precifit may cause involuntary movements and mental disturbances.

Patients with a history of severe involuntary movements or psychotic episodes when treated with levodopa alone should be observed carefully when Precifit is substituted. These reactions are thought to be due to increased brain dopamine following administration of levodopa, and use of Precifit may cause a recurrence.

At abrupt withdrawal of anti-Parkinsonian agents (especially during concomitant treatment with neuroleptics), Neuroleptic Malignant Syndrome including muscular rigidity, elevated body temperature, mental changes and elevated serum creatinine phosphokinase values have been reported.

Therefore, patients should be closely monitored if the dosage of Precifit is abruptly reduced or the treatment is discontinued, especially when receiving concurrent treatment with neuroleptics. Levodopa has been associated with somnolence and episodes of sudden sleep onset.

Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported very rarely. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with levodopa.

Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore, a reduction of dosage or termination of therapy may be considered. Impulse control disorders Patients should be regularly monitored for the development of impulse control disorders.

Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa including Precifit.

Review of treatment is recommended if such symptoms develop. Concomitant administration of antipsychotics with dopamine receptor blocking properties, particularly D2 receptor antagonists should be carried out with caution, and the patient carefully observed for loss of antiparkinsonian effect or worsening of parkinsonian symptoms.

Patients with a history of convulsions should be treated with caution. As with levodopa, periodic evaluation of hepatic, haematopoetic, cardiovascular and renal function are recommended during extended therapy. Patients with chronic wide-angle glaucoma may be treated cautiously with Precifit provided the intra-ocular pressure is well controlled and the patient monitored carefully for changes in intra-ocular pressure during therapy.

If general anaesthesia is required, therapy with Precifit may be continued for as long as the patient is permitted to take fluids and medication by mouth. If therapy has to be stopped temporarily, carbidopa/levodopa may be restarted as soon as oral medication can be taken at the same daily dosage as before.

Epidemiological studies have shown that patients with Parkinson's disease have a higher risk of developing melanoma than the general population (approximately 2-6 fold higher). It is unclear whether the increased risk observed was due to Parkinson's disease, or other factors such as medicinal products used to treat Parkinson's disease.

Therefore, patients and providers are advised to monitor for melanomas on a regular basis when using Precifit for any indication. Periodic skin examinations performed by appropriately qualified individuals such as dermatologists, should be considered.

Dopamine Dysregulation Syndrome (DDS) is an addictive disorder resulting in excessive use of the product seen in some patients treated with carbidopa/levodopa. 8). Effect on laboratory tests Commonly, levels of blood urea nitrogen, creatinine, and uric acid are lower during administration of carbidopa/levodopa than with levodopa.

Transient abnormalities include elevated levels of blood urea, AST (SGOT), ALT (SGPT), LDH, bilirubin, and alkaline phosphatase. Decreased haemoglobin, haematocrit, elevated serum glucose and white blood cells, bacteria and blood in the urine have been reported.

Positive Coombs' tests have been reported, both with carbidopa/levodopa and levodopa alone. Precifit may cause a false positive result when a dipstick is used to test for urinary ketone; and this reaction is not altered by boiling the urine.

The use of glucose oxidase methods may give false negative results for glycosuria.

1. Non-selective monoamine oxidase (MAO) inhibitors and selective MAO type A inhibitors are contraindicated for use with Precifit. These inhibitors must be discontinued at least two weeks before starting therapy with Precifit. g. selegiline hydrochloride).

) Precifit is contraindicated in patients with narrow-angle glaucoma. Since levodopa may activate a malignant melanoma, it should not be used in patients with suspicious undiagnosed skin lesions or a history of melanoma. g. pheochromocytoma, hyperthyroidism, Cushing's syndrome, as well as psychosis.